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A rapid ex vivo tissue model for optimising drug detection and ionisation in MALDI imaging studies

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Abstract

The aim of this study was to establish an ex vivo model for a faster optimisation of sample preparation procedures, for example matrix choice, in matrix-assisted laser desorption/ionisation (MALDI) drug imaging studies. The ionisation properties of four drugs, afatinib, erlotinib, irinotecan and pirfenidone, were determined in an ex vivo tissue experiment by spotting decreasing dilution series onto liver sections. Hereby, the drug signals were distinctly detectable using different matrix compounds, which allowed the selection of the optimal matrix for each drug. The analysis of afatinib and erlotinib yielded high drug signals with α-cyano-4-hydroxycinnamic acid matrix, whereas 2,3-dihydroxybenzoic acid was identified as optimal matrix for irinotecan and pirfenidone detection. Our method was validated by a MALDI drug imaging approach of in vivo treated mouse tissue resulting in corresponding findings, indicating the spotting method as an appropriate approach to determine the matrix of choice. The present study shows the accordance between the detection of ex vivo spotted drugs and in vivo administered drugs by MALDI-TOF and MALDI-FT-ICR imaging, which has not been demonstrated so far. Our data suggest the ex vivo tissue spotting method as an easy and reliable model to optimise MALDI imaging measurements and to predict drug detection in tissue sections derived from treated mice prior to the recruitment of laboratory animals, which helps to save animals, time and costs.

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Acknowledgments

We thank Jolanta Slawska for excellent technical assistance. The study was supported by Ministry of Education and Research of the Federal Republic of Germany (BMBF) (Grant Nos. 01IB10004E, 01ZX1310B), the Deutsche Forschungsgemeinschaft (Grant Nos. HO 1258/3-1, SFB 824 TP Z02 and WA 1656/3-1) to AW and SFB 824 C5 to UK, and Helmholtz Zentrum München (TKP-Project) to OE and AW.

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Authors and Affiliations

  1. Research Unit Analytical Pathology, Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764, Neuherberg, Germany

    K. Huber, M. Aichler, N. Sun, A. Buck & A. Walch

  2. Department of Nuclear Medicine, Technische Universität München, Munich, Germany

    Z. Li

  3. Comprehensive Pneumology Center, University Hospital of the Ludwig-Maximilians-Universität and Helmholtz Zentrum München, Member of the German Center for Lung Research, Munich, Germany

    I. E. Fernandez & O. Eickelberg

  4. Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    S. M. Hauck

  5. Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    H. Zitzelsberger

  6. Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

    K. P. Janssen

  7. Department of Internal Medicine III, Technische Universität München, Munich, Germany

    U. Keller

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  1. K. Huber
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  2. M. Aichler
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  3. N. Sun
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  4. A. Buck
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  5. Z. Li
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  6. I. E. Fernandez
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  7. S. M. Hauck
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  8. H. Zitzelsberger
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  9. O. Eickelberg
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  10. K. P. Janssen
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  11. U. Keller
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  12. A. Walch
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Corresponding author

Correspondence to A. Walch.

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Huber, K., Aichler, M., Sun, N. et al. A rapid ex vivo tissue model for optimising drug detection and ionisation in MALDI imaging studies. Histochem Cell Biol 142, 361–371 (2014). https://doi.org/10.1007/s00418-014-1223-0

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  • DOI: https://doi.org/10.1007/s00418-014-1223-0

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